AB0496 SHOULD ANTIBODIES TO DOMAIN I B2-GLYCOPROTEIN 1 BE INVESTIGATED IN PATIENTS WITH ANTIPHOSPHOLIPID SYNDROME (APS) AND SYSTEMIC LUPUS ERYTHEMATOSUS (SLE)?
Authors: F. Cheldieva, T. Reshetnyak, M. Cherkasova, S. Glukhova, A. Lila, E. Nasonov
Journal: Annals of the Rheumatic Diseases (2022)

Background The role of antiphospholipid antibodies (aPL) not included in the International Classification Criteria for the verification of APS continues to be discussed. Objectives To determine the clinical significance of IgG antibody for domain 1 β 2 -glycoprotein 1 (IgG-aβ 2 -GP1-D1) in patients with APS and SLE. Methods The study included 187 patients: 52 - with primary APS (PAPS), 12 - with probable APS (proAPS), 59 - with SLE+APS, and 64 - with SLE without APS. The comparison group included 49 patients with various rheumatic diseases (thrombosis without aPL (n=7), rheumatoid arthritis (RA) (n=10), Behcet’s disease (BD) (n=15), systemic sclerosis (SSD) (n=12), pregnant women (n=2), polymyositis (n=2) and Buerger’s endarteritis (n=1)) and a control group of 100 relatively healthy people. IgG/IgM-antibodies to cardiolipin (aCL) and IgG/IgM-aβ 2 -GP1 were determined by ELISA, and IgG-aβ 2 -GP1-D1 - by chemiluminescence assay (CMA) in all patients and controls. Results IgG-aβ 2 -GP1-D1 was detected in 37 (71%) of 52 patients with primary APS (PAPS), in 6 (50%) of 12 patients with probable APS (proAPS), in 42 (71%) of 59 patients with SLE+APS, in 17 (26%) of 64 patients with SLE, in 1 (2%) of comparison group and in none of control group. IgG-aβ 2 -GP1-D1 was significantly associated with PAPS and SLE+APS compared with patients with SLE (P=0,0002 and P=0,0001, respectively). IgG-aβ 2 -GP1-D1 levels were significantly higher in patients with PAPS, proAPS, SLE+APS, and SLE compared to control group (P &lt; 0,000001, 0,03, &lt; 0,000001, and 0,02, respectively). IgG-aβ 2 -GP1-D1 levels were significantly higher in patients with PAPS and SLE+APS compared to patients with SLE (P = 0,001 and P = 0,000005, respectively) and patients from the comparison group (P &lt; 0,05). The frequence of IgG-aβ 2 -GP1-D1 positivity was associated with both thrombosis and obstetric pathology - the risk of developing clinical manifestations of APS was 9,69 and 4,19 times higher, respectively. A reliable correlation between antibodies to IgG-aβ 2 -GP1-D1 and arterial thrombosis can be traced. Obstetric pathology was detected in 32 of 37 women with a history of pregnancy and all were with IgG-aβ 2 -GP1-D1, versus 21 of 32 with negative IgG-aβ 2 -GP1-D1 (χ2=4,19; P=0,04). Eclampsia/preeclampsia and fetoplacental insufficiency in history was in 19 of 37 women with IgG-aβ 2 -GP1-D1, versus 7 of 32 with obstetric pathology but no IgG-aβ 2 -GP1-D1 (χ 2=6,35; P=0,01). The incidence of obstetric pathology was significantly associated with the presence of IgG-aβ 2 -GP1-D1 compared to women without these antibodies. Isolated IgG-aβ 2 -GP1-D1 positivity was reported in 13 (19%) of 70 aPL-negative patients. Obstetric pathology was present in all 6 (100%) women who had pregnancy in their disease course, and thrombosis in 7 (53%) of 13 patients. Sensitivity and specificity of IgG-aβ 2 -GP1-D1 depending on APS and its clinical manifestations are presented in the Table 1. Table 1. Sensitivity and specificity of IgG-aβ 2 -GP1-D1 Thrombosis Obstetric pathology Diagnosis of APS Sensitivity (%) 63 58 71 Specificity (%) 83 92 87 Conclusion The frequency of IgG-aβ 2 -GP1-D1 positivity was higher in patients with APS compared to patients with SLE without aPL, comparison group and controls (P &lt; 0,05). In 19% of cases, isolated IgG-aβ 2 -GP1-D1 positivity was observed. Positive IgG-aβ 2 -GP1-D1 levels were significantly associated with thrombotic complications and with obstetric pathology (χ2=8,84; P=0,002 and χ2=6,35; P=0,01). Specificity of IgG-aβ 2 -GP1-D1 for APS and its clinical manifestations (thrombosis and obstetric pathology) was higher than sensitivity. The study was performed at the V.A. Nasonova Research Institute of Rheumatology within the framework of the fundamental topic FURS-2022-003. Disclosure of Interests None declared